Effects of herbal dregs supplementation of Salvia miltiorrhiza and Isatidis Radix residues improved production performance and gut microbiota abundance in late-phase laying hens.

The present study was designed to evaluate the effect of a mixture of Chinese medicinal residues (CMRs) consisting of Salvia miltiorrhiza residues (SMR) and Isatidis Radix residues (IRR) on productive performance, egg quality, serum lipid and hormone levels, liver and blood antioxidant capacity, oviduct inflammation levels, and gut microbiota in the late-laying stage. A total of 288 fifty-four-week-old BaShang long-tailed hens were divided into four groups. The feed trial period was 8 weeks. The control group was fed the basic diet as a CCMR group, supplemented with 3, 4, and 6% for the experimental groups LCMR, MCMR, and HCMR. The egg production rate of the MCMR group was 8.1% higher than that of the CCMR group (p < 0.05). Serum triglyceride (TG) levels of hens of the CMR-supplemented group were significantly decreased than those of the CCMR group (p < 0.05). The group supplemented with different levels of CMR had significantly higher serum HDL-C levels compared with the control group (p < 0.05). Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were remarkably increased for the LCMR and MCMR groups and significantly decreased for the HCMR group compared to CCMR (p < 0.05). Serum and liver glutathione peroxidase (GSH-PX) activities were significantly increased, and malondialdehyde (MDA) levels were significantly decreased in the MCMR group compared to the CCMR group (p < 0.05). The expression levels of tubal inflammatory factor markers (IL-4, IL-1ß, TNF-α) in the MCMR and HCMR groups were consistent with the pathological findings of the sections. As for cecal microbiota, supplementation with CMR affected the alpha diversity of the cecum microbiome at the genus level. The Shannon index was significantly higher in the MCMR group than in the CCMR and HCMR groups (p < 0.05). Supplementation with different levels of CMR mainly regulated the ratio of intestinal Firmicutes to Bacteroidetes and the abundance of phyla such as Proteobacteria. In addition, CMR supplementation at different levels in the diet enriched lipid-metabolizing bacteria, such as Bacteroides and Ruminococcus_gnavus_group. Furthermore, according to linear discriminant analysis (LDA) effect size (LEfSe) analysis, the MCMR group showed an increase in the number of short-chain fatty acid-producing bacteria Romboutsia and fiber-degrading specialized bacteria Monoglobus. Therefore, supplementation of appropriate amounts of CMR to the diet of laying hens enhanced reproductive hormone levels, hepatic antioxidant capacity, and lipid metabolism, alleviated the levels of oviductal inflammatory factors, and modulated the abundance structure of bacterial flora to improve the late-laying performance and egg quality. The results of the current study showed that CMR is a beneficial feed supplement for chickens when added in moderation.

A novel isoquinoline alkaloid HJ-69 isolated from Zanthoxylum bungeanum attenuates inflammatory pain by inhibiting voltage-gated sodium and potassium channels.

ETHNOPHARMACOLOGY RELEVANCE: Zanthoxylum bungeanum Maxim. (Z. bungeanum), a member of the Rutaceae family, has a rich history of traditional use in Asia for treating arthritis and toothache conditions. As characteristic chemical components, numerous kinds of alkaloids have been extracted from plants and their diverse biological activities have been reported. However, research on the isoquinoline alkaloid, a specific type of alkaloids, in Z. bungeanum was scarce. AIM OF THE STUDY: The study aimed to isolate a novel isoquinoline alkaloid from Z. bungeanum and explore its pharmacological activity in vitro and analgesic activity in vivo. MATERIALS AND METHODS: Isoquinoline alkaloid isolation and identification from Z. bungeanum were conducted using chromatographic and spectroscopic methods. The whole-cell patch-clamp technique was applied to assess its impact on neuronal excitability, and endogenous voltage-gated potassium (Kv) and sodium (Nav) currents in acutely isolated mouse small-diameter dorsal root ganglion (DRG) neurons. Its inhibitory impacts on channels were further validated with HEK293 cells stably expressing Nav1.7 and Nav1.8, and Chinese hamster ovary (CHO) cells transiently expressing Kv2.1. The formalin inflammatory pain model was utilized to evaluate the potential analgesic activity in vivo. RESULTS: A novel isoquinoline alkaloid named HJ-69 (N-13-(3-methoxyprop-1-yl)rutaecarpine) was isolated and identified from Z. bungeanum for the first time. HJ-69 significantly suppressed the firing frequency and amplitudes of action potentials in DRG neurons. Consistently, it state-dependently inhibited endogenous Nav currents of DRG neurons, with half maximal inhibitory concentration (IC50) values of 13.06 ± 2.06 µM and 30.19 ± 2.07 µM for the inactivated and resting states, respectively. HJ-69 significantly suppressed potassium currents in DRG neurons, which notably inhibited the delayed rectifier potassium (IK) currents (IC50 = 6.95 ± 1.29 µM) and slightly affected the transient outward potassium (IA) currents (IC50 = 523.50 ± 39.16 µM). Furtherly, HJ-69 exhibited similar potencies on heterologously expressed Nav1.7, Nav1.8, and Kv2.1 channels, which correspondingly represent the main components in neurons. Notably, intraperitoneal administration of 30 mg/kg and 100 mg/kg HJ-69 significantly alleviated pain behaviors in the mouse inflammatory pain model induced by formalin. CONCLUSION: The study concluded that HJ-69 is a novel and active isoquinoline alkaloid, and the inhibition of Nav and Kv channels contributes to its analgesic activity. HJ-69 may be a promising prototype for future analgesic drug discovery based on the isoquinoline alkaloid.

Rapid evaluation of PHD2 inhibitory activity of natural products based on capillary electrophoresis online stacking strategy.

Prolyl hydroxylase domain 2 (PHD2) is an important enzyme in the human body that perceives changes in oxygen concentration and regulates response in hypoxic environments. Evaluation of PHD2 inhibitory activity of natural products is crucial for drug development of hypoxia related diseases. At present, the detection of low concentration of α-ketoglutaric acid (the substrate of PHD2 enzymatic reaction) requires derivatization reactions or sample pretreatment, which undoubtedly increases the workload of PHD2 inhibitory activity evaluation. In this paper, a direct detection approach of α-ketoglutaric acid was established by using the online stacking strategy of capillary electrophoresis to evaluate the PHD2 inhibitory activity of natural products. Under optimized conditions, detection of a single sample can be achieved within 2 min. By calculation, the intraday precision RSD of the apparent electrophoretic mobility and peak areas of α-ketoglutaric acid are 0.92 % and 0.79 %, respectively, and the interday RSD were 1.27 % and 0.96 % respectively. The recoveries of the present approach were 97.9-105.2 %, and the LOQ and LOD were 2.0 µM and 5.0 µM, respectively. Furthermore, this approach was applied for the evaluation of inhibitory activity of PHD2 for 13 natural products, and PHD2 inhibitory activity of salvianolic acid A was firstly reported. The present work not only realizes evaluation of PHD2 inhibitory activity through direct detection of α-ketoglutaric acid, but also provides technical support for the discovery of potential drug molecules in hypoxia related diseases.

Efficacy and safety of Gushen Antai Pills combined with dydrogesterone in the treatment of threatened miscarriage: a systematic review and meta-analysis.

Background: Despite some progress has been made in the pathogenesis and treatment of threatened miscarriage (TM), conventional treatment remains suboptimal. Thus, complementary medicine gradually become a new treatment option for treating threatened miscarriage. Gushen Antai Pills (GAP), a classic prescription of Traditional Chinese medicine (TCM), has became a popular complementary therapy to conventional western medicine (dydrogesterone) in treating threatened miscarriage in recent years. However, a systematic summary and analysis for its therapeutic effects is lacking. This meta-analysis aimed to systematically evaluate the effectiveness and safety of Gushen Antai Pills combined with dydrogesterone in the treatment of threatened miscarriage. Methods: A systematic search across seven electronic databases was conducted from inception to 17 September 2022. Studies were included if they were randomized controlled trials (RCTs) evaluating the effect of integrating Gushen Antai Pills and dydrogesterone in patients with threatened miscarriage, and reported the outcomes of interest. All statistical analyses were conducted using the Revman5.3 and Stata 13 software. The GRADE system was used to evaluate the quality of evidence. Results: Ten eligible randomized controlled trials involving 950 participants were contained in this meta-analysis. The pooled analysis showed that Gushen Antai Pills combined with dydrogesterone can significantly reduce the incidence of early pregnancy loss (RR: 0.29; 95% CI: 0.19-0.42; p < 0.00001) and alleviate clinical symptoms (RR: 1.39; 95% CI: 1.22-1.59; p < 0.00001), compared with treatment of dydrogesterone alone. Also, meta-analysis indicated that integrating Gushen Antai Pills and dydrogesterone is more effective than using dydrogesterone alone in improving hormone levels (serum levels of progesterone, ß-HCG and estradiol) for women with threatened miscarriage (all p < 0.00001). Meanwhile, the combined effects with significant heterogeneity also showed favorable consistency in the sensitivity analyses, indicating a good stability of present results. Moreover, no significant differences between Gushen Antai Pills combined with dydrogesterone and control group on adverse events was identified. The overall GRADE qualities were low to moderate. Conclusion: The overall available evidence suggested that Gushen Antai Pills combined with dydrogesterone had significant effects in improving pregnancy success rate, clinical symptoms and hormone levels for women with threatened miscarriage, with considerable safety and reliability. However, due to the partial heterogeneity, suboptimal quality and high risk of bias of some included studies, further rigorously designed randomized controlled trials are required. Systematic Review Registration: identifier https://INPLASY2022120035, https://inplasy.com/inplasy-2022-12-0035/.

Alkylamides from Zanthoxylum armatum DC. and their neuroprotective activity.

Zanthoxylum armatum DC. is an important medicinal plant, and its pericarps are commonly used as a natural spice in Asian countries. In this study, fifteen alkylamides were isolated and elucidated from the pericarps of Z. armatum, including five undescribed alkylamides (1-5) and ten known compounds (6-15). The molecular structures of all compounds were elucidated by 1D and 2D NMR spectroscopic analysis and mass spectrometry, among which the absolute configuration of compound 15 was determined by the Mo2(OAc)4-induced circular dichroism method. Moreover, all compounds were screened for their neuroprotective activity against H2O2-induced oxidative stress in human neuroblastoma SH-SY5Y cells for the evaluation of their neuroprotective activity. Especially, compounds 2-4 expressed potential neuroprotective activity, and further research showed that the cell viability was significantly enhanced in a concentration dependent manner when the cells were treated for 6 h. Moreover, compounds 2-4 could decrease reactive oxygen species accumulation. This paper enriched structure types of alkylamides in Zanthoxylum armatum.

Gymnadenia conopsea (L.) R. Br.: Comprehensive review of propagation and breeding, traditional uses, chemical composition, pharmacology, quality control, and processing.

ETHNOPHARMACOLOGICAL RELEVANCE: Gymnadenia conopsea, a perennial herbaceous flowering plant that belongs to the family of Orchidaceae, sporadic distributed in the altitudes of 200-4700 m across northern Europe and, temperate and subtropical Asia region. The dried tubers of G. conopsea have been used to treat cough, asthma, and their syndromes, and also as a tonic in China and surrounding countries for a long history. G. conopsea is often processed deeply processed before use to enhance its efficacy. In recent years, because of its remarkable pharmacological activity and health care function, G. conopsea has been used more and more widely. Due to its extensive application and bad growth environment, the wild distribution of G. conopsea is decreasing and it has been listed as an endangered plant. AIM OF THE REVIEW: This review aims to summarize the propagation and breeding, traditional uses, chemical composition, pharmacology, quality control, and processing of G. conopsea. Moreover, it also provides suggestions for the future high-value utilization of G. conopsea. MATERIALS AND METHODS: A literature search on Gymnadenia genus and G. conopsea was performed using scientific databases including SciFinder, ACS, Web of Science, Springer, ScienceDirect, PubMed, and CNKI. Information was also collected from classic books of Chinese herbal medicine, official websites, Ph.D. and M.Sc. Dissertations, and so on. Structures of chemical compounds were drawn by ChemDraw software. RESULTS: As of submission date of this manuscript, total 170 natural compounds have been isolated and characterized from G. conopsea, and all of the compounds were isolated from the tubers. The isolated compounds including benzylester glucosides, dihydrostilbenes, phenanthrenes, phenolic compounds, alkaloids, polysaccharide, lignans, flavones, triterpenoids, steroids, and other compounds. Some of these compounds and active extracts exhibited a wide range of pharmacological activities, in which, the tonifying, anti-fatigue, anti-oxidant, anti-viral, sedative and hypnotic activities are consistent with the traditional uses for the treatment of diseases. In addition, a variety of new pharmacological activities, such as preventing and treating gastric ulcers, immunoregulatory, anti-hyperlipidemia, anti-anaphylaxis, anti-silicosis, anti-cancer and neuroprotective activities have also been reported. However, the bioactive compounds responsible for most of the above pharmacological effects have not been well summarised till now. In this manuscript, analysis, speculation and summary of compounds that responsible for pharmacological effects were conducted. CONCLUSIONS: The chemical constituents and pharmacological activities studies of G. conopsea extract have been summarised in this context, the isolated compounds responsible for the pharmacological activities were also analyzed and deduced according to the publications, all above led to suggestions for the future high-value utilization of G. conopsea.

Effects of Lactobacillus plantarum and Pediococcus acidilactici co-fermented feed on growth performance and gut microbiota of nursery pigs.

The fermented feed has been used extensively as a growth promoter in agricultural animal production. However, the effects of fermented feed on swine gut microbiota are still largely unknown. The work presented here aimed to investigate the growth performance and gut microbiota of nursery pigs receiving the LPF diet (10% Lactobacillus plantarum and Pediococcus acidilactici co-fermented feed + basal diet) compared with pigs receiving the NC diet (basal diet). The data showed LPF diet numerically improved average daily gain and significantly increased fecal acetate, butyrate, and total short-chain fatty acid (SCFA) concentrations. Furthermore, gut microbiota structure and membership significantly changed in response to the addition of fermented feed in the diet. Gut microbiota results indicated that LPF treatment significantly enriched SCFA-producing bacteria such as Megasphaera, Roseburia, Faecalibacterium, Blautia, Selenomonas, Dialister, Acidaminococcus, Ruminococcus, and Bifidobacterium. Some of these bacteria also had anti-inflammatory and other beneficial functions. Overall, these findings suggested that Lactobacillus plantarum and Pediococcus acidilactici co-fermented feed benefited growth performance and established potential health impacts on the gut microbiota of nursery pigs.

Gypenosides (GPs) alleviates hypoxia-induced injury in PC12 cells and enhances tolerance to anoxia in C57BL/6 mice.

Oxygen is a necessary substance for life activities, but reduced oxygen utilization due to high altitude exposure and respiratory dysfunction diseases could lead to pathological changes in the organisms. Herein gypenosides, the active ingredients in the food and medicine resource plant Gynostemma pentaphyllum (Thunb.) Makino were found to alleviate hypoxia-induced injury in PC12 cells. Moreover, hypoxia induced an increase in Ca2+ and reactive oxygen species content, and such patterns were both significantly reduced by gypenosides treatment. At the same time, gypenosides significantly blocked the decrease of both NO content and mitochondrial membrane potential caused by hypoxia. Furthermore, gypenosides gavage treatment significantly prolonged the survival time of C57BL/6 mice in confinement up to 24.3% and enhanced the locomotor ability of mice. Therefore, gypenosides have good neuroprotective effects and hypoxia tolerance activity and have the prospect of being developed as a preventive and therapeutic drug for hypoxia-related diseases. PRACTICAL APPLICATIONS: Gypenosides can enhance tolerance of cells and mice to hypoxia and have the potential to be developed into hypoxia-resistant health food and drugs.

Dammarane triterpenoids with rare skeletons from Gynostemma pentaphyllum and their cytotoxic activities.

Three unreported dammarane-type triterpenoids with rare skeletons (1-3), along with one undescribed gypenoside (4), were isolated from the aerial parts of Gynostemma pentaphyllum using diverse chromatographic materials and pre-HPLC. Their structures were elucidated on the basis of spectroscopic and spectrometric data, while the absolute configurations of 1-3 were assessed via electronic circular dichroism (ECD) analyses. Notably, compounds 1-3 possess a 3,19-hemiketal bridge in the A ring. Saponin 4 possesses an unreported 20,25-oxa structural moiety. Their antiproliferative effects against HepG2, MCF-7, and DU145 cell lines were screened. Compounds 1-3 displayed moderate cytotoxicity with IC50 values ranging from 13.7 ± 0.2 to 32.0 ± 1.7 µM.

Terpenoids from Nardostachys jatamansi and their cytotoxic activity against human pancreatic cancer cell lines.

Five previously unreported terpenoids, together with fifteen known analogs, were isolated from a methanol extract of the roots and rhizomes of Nardostachys jatamansi. Their structures, including absolute configurations, were elucidated by spectroscopic data and electronic circular dichroism (ECD) spectra analyses, as well as single-crystal X-ray diffraction for crystalline compounds. Structurally, (4R,5S,6S,7R)-1(10)-aristolane-8,9-diacid is a novel 8,9-dicarboxylic acid derivative of aristolane-type sesquiterpenoid. (4R,6S,7R,10S)-10-Hydroxyguaia-1(5)-6,7-epoxy-2-one is an undescribed analogue of nardoguaianone K, with a rare 6,7-epoxide group. (4R,5R,6R,8R)-1(10)-Isonardosinone-8-ol-9-one-7,11-lactone is an isonardosinane-type sesquiterpene bearing a γ-lactone ring. Dinardokanshone F is a rare example of a sesquiterpene dimer from N. jatamansi connected by an oxo bridge. The isolates were evaluated for their cytotoxic activity against four human pancreatic cancer cell lines (CFPAC-1, PANC-1, CAPAN-2 and SW1990). Compound epoxynardosinone exhibited significant cytotoxicity against CAPAN-2 cell lines with IC50 value of 2.60 ± 1.85 µM. 1-Hydroxylaristolone displayed comparable cytotoxicity on CFPAC-1 cell lines (IC50 1.12 ± 1.19 µM), compared to Taxol (IC50 0.32 ± 0.13 µM). 1-Hydroxylaristolone, 1(10)-aristolane-9ß-ol, 1(10)-aristolen-2-one, alpinenone, valtrate isovaleroyloxyhydrine and nardostachin displayed stronger cytotoxicity against PANC-1 cell lines with IC50 values ranging from 0.01 ± 0.01 to 6.50 ± 1.10 µM. 1(10)-Aristolane-9ß-ol, 10-hydroxyguaia-1(5)-6,7-epoxy-2-one, nardoguaianone K, nardonoxide, epoxynardosinone, 1(10)-isonardosinone-8-ol-9-one-7,11-lactone, valtrate isovaleroyloxyhydrine and nardostachin showed remarkable cytotoxicity against SW1990 cell lines with IC50 values ranging from 0.07 ± 0.05 to 4.82 ± 6.96 µM. Furthermore, the primary mechanistic study of nardostachin demonstrated that it induced cell apoptosis via the mitochondria-dependent pathway, and induced SW1900 cell arrest at G2/M phase.

(-)-Naringenin 4',7-dimethyl Ether Isolated from Nardostachys jatamansi Relieves Pain through Inhibition of Multiple Channels.

(-)-Naringenin 4',7-dimethyl ether ((-)-NRG-DM) was isolated for the first time by our lab from Nardostachys jatamansi DC, a traditional medicinal plant frequently used to attenuate pain in Asia. As a natural derivative of analgesic, the current study was designed to test the potential analgesic activity of (-)-NRG-DM and its implicated mechanism. The analgesic activity of (-)-NRG-DM was assessed in a formalin-induced mouse inflammatory pain model and mustard oil-induced mouse colorectal pain model, in which the mice were intraperitoneally administrated with vehicle or (-)-NRG-DM (30 or 50 mg/kg) (n = 10 for each group). Our data showed that (-)-NRG-DM can dose dependently (30~50 mg/kg) relieve the pain behaviors. Notably, (-)-NRG-DM did not affect motor coordination in mice evaluated by the rotarod test, in which the animals were intraperitoneally injected with vehicle or (-)-NRG-DM (100, 200, or 400 mg/kg) (n = 10 for each group). In acutely isolated mouse dorsal root ganglion neurons, (-)-NRG-DM (1~30 µM) potently dampened the stimulated firing, reduced the action potential threshold and amplitude. In addition, the neuronal delayed rectifier potassium currents (IK) and voltage-gated sodium currents (INa) were significantly suppressed. Consistently, (-)-NRG-DM dramatically inhibited heterologously expressed Kv2.1 and Nav1.8 channels which represent the major components of the endogenous IK and INa. A pharmacokinetic study revealed the plasma concentration of (-)-NRG-DM is around 7 µM, which was higher than the effective concentrations for the IK and INa. Taken together, our study showed that (-)-NRG-DM is a potential analgesic candidate with inhibition of multiple neuronal channels (mediating IK and INa).

A bioactive gypenoside (GP-14) alleviates neuroinflammation and blood brain barrier (BBB) disruption by inhibiting the NF-κB signaling pathway in a mouse high-altitude cerebral edema (HACE) model.

BACKGROUND: Neuroinflammation caused by peripheral lipopolysaccharides (LPS) under hypoxia is a key contributor to the development of high altitude cerebral edema (HACE). Our previous studies have shown that gypenosides and their bioactive compounds prevent hypoxia-induced neural injuries in vitro and in vivo. However, their effect on neuroinflammation-related HACE remains to be illustrated. The present study aimed to investigate the effects of GP-14 in HACE mouse model. METHODS: HACE mice were treated with GP-14 (100 and 200 mg/kg) for 7 days. After the treatments, the level of serum inflammation cytokines and the transcription of inflammatory factors in brain tissue were determined. The activation of microglia, astrocyte and the changes of IgG leakage and the protein levels of tight junction proteins were detected. Furthermore, the inflammatory factors and nuclear factor-κB (NF-κB) signaling pathway in BV-2 cells and primary microglia were detected. RESULTS: GP-14 pretreatment alleviated both the serum and neural inflammatory responses caused by LPS stimulation combined with hypobaric hypoxia exposure. In addition, GP-14 pretreatment inhibited microglial activation, accompanied by a decrease in the M1 phenotype and an increase in the M2 phenotype. Moreover, the disruption of the blood brain barrier (BBB) integrity, including increased IgG leakage and decreased expression of tight junction proteins, was attenuated by GP-14 pretreatment. Based on the BV-2 and primary microglial models, the inflammatory response and activation of the NF-κB signaling pathway were also inhibited by GP-14 pretreatment. CONCLUSION: Taken together, our results demonstrated that GP-14 exhibited prominent protective roles against neuroinflammation and BBB disruption in a mouse HACE model. GP-14 could be a potential choice for the treatment of HACE in the future.

The Clinical Efficacy and Safety of Enhanced Recovery After Surgery for Cesarean Section: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Observational Studies.

Background: Enhanced recovery after surgery (ERAS) has been adopted in some maternity units and studied extensively in cesarean section (CS) in the last years, showing encouraging results in clinic practice. However, the present evidence assessing the effectiveness of ERAS for CS remains weak, and there is a paucity in the published literature, especially in improving maternal outcomes. Our study aimed to systematically evaluate the clinical efficacy and safety of ERAS protocols for CS. Methods: A systematic literature search using Embase, PubMed, and the Cochrane Library was carried out up to October 2020. The appropriate randomized controlled trials (RCTs) and observational studies applying ERAS for patients undergoing CS were included in this study, comparing the effect of ERAS protocols with conventional care on length of hospital stay (LOS), readmission rate, incidence of postoperative complications, postoperative pain score, postoperative opioid use, and cost of hospitalization. All statistical analyses were conducted with the RevMan 5.3 software. Results: Ten studies (four RCTs and six observational studies) involving 16,391 patients were included. ERAS was associated with a decreased LOS (WMD -7.47 h, 95% CI: -8.36 to -6.59 h, p < 0.00001) and lower incidence of postoperative complications (RR: 0.50, 95% CI: 0.37 to 0.68, p < 0.00001). Moreover, pooled analysis showed that postoperative pain score (WMD: -1.23, 95% CI: -1.32 to -1.15, p < 0.00001), opioid use (SMD: -0.46, 95% CI: -0.58 to -0.34, p < 0.00001), and hospital cost (SMD:-0.54, 95% CI: -0.63 to -0.45, p < 0.00001) were significantly lower in the ERAS group than in the conventional care group. No significant difference was observed with regard to readmission rate (RR: 0.86, 95% CI: 0.48 to 1.54, p = 0.62). Conclusions: The available evidence suggested that ERAS applying to CS significantly reduced postoperative complications, lowered the postoperative pain score and opioid use, shortened the hospital stay, and potentially reduced hospital cost without compromising readmission rates. Therefore, protocols implementing ERAS in CS appear to be effective and safe. However, the results should be interpreted with caution owing to the limited number and methodological quality of included studies; hence, future large, well-designed, and better methodological quality studies are needed to enhance the body of evidence.

Narjatamolide, an Unusual Homoguaiane Sesquiterpene Lactone from Nardostachys jatamansi.

Narjatamolide (1), an unusual homoguaiane sesquiterpene lactone, was isolated from the roots and rhizomes of Nardostachys jatamansi DC. It represents the new carbon skeleton of a homoguaiane sesquiterpenoid possessing an additional acetate unit spiro-fused with C-4 and C-15 to form a cyclopropane ring. The structure of 1 was elucidated by extensive spectroscopic analyses, and the absolute configuration was confirmed by the electronic circular dichroism (ECD) calculations and X-ray single-crystal diffraction analysis. Compound 1 showed antiproliferative effects against BEL-7402 cell lines with an IC50 value of 5.67 ± 1.43 µM, and the mechanism study showed that 1 induces cell cycle of BEL-7402 cell lines arrest at G2/M phase.

Efficacy and safety of nintedanib in Asian patients with systemic sclerosis-associated interstitial lung disease: Subgroup analysis of the SENSCIS trial.

BACKGROUND AND OBJECTIVE: In the SENSCIS trial in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), nintedanib reduced the rate of decline in forced vital capacity (FVC) (mL/year) over 52 weeks by 44% in comparison with placebo, with manageable adverse events in most patients. We analyzed the efficacy and safety of nintedanib in patients of Asian race. METHODS: Patients with SSc-ILD were randomized to receive nintedanib or placebo. The outcomes over 52 weeks were analyzed in Asian versus non-Asian patients. RESULTS: Of the 288 patients in each treatment group, 62 (21.5%) in the nintedanib group and 81 (28.1%) in the placebo group were Asian; 90.2% of the Asian patients were enrolled in Asian countries. In the placebo group, the rate of FVC decline over 52 weeks was consistent between Asian and non-Asian patients (-99.9 and -90.6 mL/year, respectively). The effect of nintedanib on reducing the rate of FVC decline over 52 weeks was consistent between Asian (difference, 44.3 mL/year [95% CI: -32.8, 121.4]) and non-Asian patients (difference, 39.0 mL/year [95% CI: -5.1, 83.1]) (treatment-by-time-by-subgroup interaction, p = 0.91). Diarrhea was the most frequent adverse event and was reported in similar proportions of Asian and non-Asian patients in the nintedanib group (80.6% and 74.3%, respectively) and placebo group (28.4% and 32.9%, respectively). CONCLUSIONS: In patients with SSc-ILD, nintedanib had a consistent benefit on slowing the progression of SSc-ILD in Asian and non-Asian patients, with a similar adverse event profile. TRIAL REGISTRATION: ClinicalTrials.gov NCT02597933.

Bungsteroid A: One Unusual C34 Pentacyclic Steroid Analogue from Zanthoxylum bungeanum Maxim.

Bungsteroid A (1), possessing an unreported carbon skeleton, was isolated from the pericarps of Zanthoxylum bungeanum Maxim. It represents the first carbon skeleton of a C34 steroid analogue featuring a unique 6/6/6/6/5-fused pentacyclic skeleton, which has been determined by spectroscopic methods, quantum-chemical 13C NMR, ECD calculations, and calculations of optical rotations. Bungsteroid A showed the antiproliferative effects against HepG2, MCF-7, and HeLa cell lines with the IC50 values of 56.3 ± 1.1, 64.2 ± 0.9, and 74.2 ± 1.3 µM, respectively.

Applying Serum Proteins and MicroRNA as Novel Biomarkers for Early-Stage Cervical Cancer Detection.

Recently, we have been seeing emerging applications of non-invasive approaches using serum biomarkers including miRNA and proteins in detection of multiple cancers. Currently, majority of these methods only use solitary type of biomarkers, which often lead to non-satisfactory sensitivity and specificity in clinical applications. To this end, we established a unique biomarker panel in this study, which determined both squamous cell carcinoma antigen (SCC Ag) degree and miRNA-29a, miRNA-25, miRNA-486-5p levels in blood for detection of early-stage cervical cancer. We designed our study with two phases: a biomarker discovery phase, followed by an independent validation phase. In total of 140 early-stage cervical cancer patients (i.e., AJCC stage I and II) and 140 healthy controls recruited in the biomarker discovery phase, we achieved sensitivity of 88.6% and specificity of 92.9%. To further assess the predictive power of our panel, we used it to an independent patient cohort that consisted of 60 early-stage cervical cancer individuals as well as 60 healthy controls, and successfully achieved both high sensitivity (80.0%) and high specificity (96.7%). Our study indicated combining analyses of multiple serum biomarkers could improve the accuracy of non-invasive detection of early-stage cervical cancer, and potentially serve as a new liquid biopsy approach for detecting early-stage cervical cancer.

Ingenane and jatrophane diterpenoids from Euphorbia kansui and their antiproliferative effects.

In this study, fourteen ingenane-type and nine jatrophane-type diterpenoids were isolated from Euphorbia kansui, including seven undescribed compounds. Kansuingenol A-C have the 6,7-vicinal diol moiety, and Kansuijatrophanol A and B possess the 11,12-vicinal diol moiety, both of which are rarely reported. 3,4-(Methylenedioxy) cinnamyl moiety was found for the first time in jatrophane-type diterpenoids, as shown in Kansuijatrophanol C and D. The absolute configurations of seven undescribed compounds have been analyzed and assigned by the modified Mosher's method, Mo2(OAc)4-induced circular dichroism (ICD) method, and CD exciton chirality method. All compounds were screened for their antiproliferative effects against HepG2, MCF-7 and DU145 cell lines. Regarding the HepG2 cells, Kansuijatrophanol C exhibited the most promising inhibition with the IC50 value of 9.47 ± 0.31 µM. Regarding the MCF-7 and DU145 cells, Kansuijatrophanol D exhibited the most promising inhibition with the IC50 values of 6.29 ± 0.18 and 4.19 ± 0.32 µM, respectively.

Diterpenoid Alkaloids and One Lignan from the Roots of Aconitum pendulum Busch.

Diterpenoid alkaloids have neroprotective activity. Herein, three napelline-type diterpenoid alkaloids 1-3, two aconitine-type diterpenoid alkaloids 4-5, and one isoquinline-type alkaloid 6, as well as one lignan glycoside 7, have been isolated from the roots of Aconitum pendulum Busch. Compounds 1 and 7 were new compounds, and their chemical structures were determined on the basis of nuclear magnetic resonance (NMR) spectra and mass spectrometry analysis. A ThT assay revealed that compound 2 showed significant disaggregation potency on the Aß1-42 aggregates.

An observational study of Chinese adults with relapsed/refractory Philadelphia-negative acute lymphoblastic leukemia.

AIM: Chinese adults with relapsed/refractory Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (Ph- ALL) have poor outcomes. PATIENTS & METHODS: We conducted a nationwide, retrospective, observational study to assess outcomes in this patient population. RESULTS: Of the 270 enrolled patients, 31% of patients at last salvage achieved complete remission (CR) or CR with partial hematologic recovery (CRh), with median time to CR/CRh of 30 days and median CR/CRh duration of 2.7 months. The CR/CRh rate was more favorable with earlier versus later lines of salvage (41, 24 and 17% at first, second and third or later salvages, respectively). CONCLUSION: This dataset serves as an important reference of real-world outcomes using currently available chemotherapy regimens for high-risk Chinese adults with relapsed/refractory Ph- ALL.